Organization of the human immunoglobulin V_H locus. The 957-kb DNA is represented by the four collections of thick horizontal lines with the 3′ end at the bottom right corner. V_H segments belonging to different V_H families are indicated by vertical lines of different colors with their names on the upper row. Pseudogenes and newly identified V_H segments are indicated with a P and an asterisk at the end of the name, respectively. Full height vertical lines represent V_H segments without truncation while those containing truncation at the 5′-, 3′-, and both 5′- and 3′-portions are indicated by half-height upper, lower, and middle lines, respectively. An enlarged physical map of the 39-kb DNA of the human D gene cluster is also shown. Locations of D segments of six families are shown by diamonds of different colors with their names. Eight nonimmunoglobulin genes are shown with their names by short arrows of different colors indicating the transcriptional orientation. 13 locus-specific homology units are indicated by boxes of different colors in the middle row. Different classes of sequences are shown in the lower row: (a) Alu (red), MIR (magenta); (b) LINE1 (green), LINE2 (dark green); (c) retrotransposons (yellow), retroviral and other LTRs (blue); (d) DNA transposons (black); (e) medium reiteration frequency repetitive sequences (purple); and (f) simple repeats (cyan). DNA clones covering the locus are shown at the bottom. The YAC clone Y13.3, cosmid clones M146, U22-1, U22, and M83, as well as P1 clones H10 and A1 were newly isolated in this study whereas the others have been described previously (8). The nucleotide sequence was deposited in DDBJ/GenBank/EMBL database under the accession number AB019437-AB019441.

(A) A phylogenetic tree of the human V_H segments based on their nucleotide sequence alignment. Three distinct sets of the V_H segments that correspond to V_HI, V_HII, and V_HIII subgroups (39) are separated by broken lines and indicated by Roman numerals. The seven V_H families are indicated by different colors. Groups of the V_H3 and V_H4 segments containing the 5′-truncation are circled. (B) Estimation of divergence time between 10 homologous units containing a pair of the V_H3 and V_H4 segments. The human/mouse divergence time (vertical line) is indicated in million years ago (Myr).